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Sickness behavior
Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection.Hart, B. L. (1988) "Biological basis of the behavior of sick animals". Neurosci Biobehav Rev. 12: 123-137. They usually (but not necessarily)Kent, S., Bluthe, R. M., Dantzer, R., Hardwick, A. J., Kelley, K. W., Rothwell, N. J. Vannice, J. L. (1992) "Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1". Proc Natl Acad Sci U S A. 89: 9117-9120. accompany fever and aid survival. Such illness responses include lethargy, depression, anorexia,Exton, M. S. (1997) "Infection-induced anorexia: active host defence strategy". Appetite. 29: 369-383. Murray, M. J. Murray, A. B. (1979) "Anorexia of infection as a mechanism of host defense". Am J Clin Nutr. 32: 593-596. sleepiness, hyperalgesia,Maier, S. F., Wiertelak, E. P., Martin, D. Watkins, L. R. (1993) "Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin". Brain Res. 623: 321-324. reduction in groomingDantzer, R. Kelley, K. W. (2007) "Twenty years of research on cytokine-induced sickness behavior". Brain Behav Immun. 21: 153-160 and failure to concentrate.Kelley, K. W., Bluthe, R. M., Dantzer, R., Zhou, J. H., Shen, W. H., Johnson, R. W. Broussard, S. R. (2003) "Cytokine-induced sickness behavior". Brain Behav Immun. 17 Suppl 1: S112-118. Sickness behavior is a motivational state that reorganizes the organism’s priorities to cope with infectious pathogens.Johnson, R. (2002) "The concept of sickness behavior: a brief chronological account of four key discoveries". Veterinary Immunology and Immunopathology. 87: 443-450 Elsevier It has been suggested as relevant to understanding depression, and some aspects of the suffering that occurs in cancer. History Sick animals have long been recognized by farmers as having different behavior. Initially it was thought that this was due to physical weakness that resulted from diverting energy from the body processes needed to fight infection. However, in the 1960s, it was shown that animals produced a blood carried ‘‘factor X’’ that acted upon the brain to cause this such sickness behavior.Holmes, J. E. Miller, N. E. (1963) "Effects of Bacterial Endotoxin on Water Intake, Food Intake, and Body Temperature in the Albino Rat". J Exp Med. 118: 649-658 Miller, N. (1964) "Some psychophysiological studies of motivation and of the behavioral effects of illness". Bull. Br. Psychol. Soc. 17: 1-20 Plasma concentrations of iron and zinc are lowered for this reason in fever.Weinberg, E. D. (1984) "Iron withholding: a defense against infection and neoplasia". Physiol Rev. 64: 65-102. Lowered threshold for pain ensures that an animal is attentive that it does not place pressure of injuried and inflammed tissues that might disrupt their healing. Reduced grooming is adaptive since it reduces water loss. Immune control Lipopolysaccharides trigger the immune system to produce proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor (TNF).Kent, S., Bluthe, R. M., Dantzer, R., Hardwick, A. J., Kelley, K. W., Rothwell, N. J. Vannice, J. L. (1992) "Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1". Proc Natl Acad Sci U S A. 89: 9117-9120 These peripherally released cytokines act on the brain via a fast transmission pathway involving primary input through the vegus nerves,Goehler, L. E., Gaykema, R. P., Nguyen, K. T., Lee, J. E., Tilders, F. J., Maier, S. F. Watkins, L. R. (1999) "Interleukin-1beta in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems?" J Neurosci. 19: 2799-2806 Goehler, L. E., Relton, J. K., Dripps, D., Kiechle, R., Tartaglia, N., Maier, S. F. Watkins, L. R. (1997) "Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication". Brain Res Bull. 43: 357-364 and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission.Konsman, J. P., Kelley, K. Dantzer, R. (1999) "Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain". Neuroscience. 89: 535-548 Peripheral cytokines may enter directly the brain.Banks, W. A., Kastin, A. J. Gutierrez, E. G. (1994) "Penetration of interleukin-6 across the murine blood-brain barrier". Neurosci Lett. 179: 53-56 Banks, W. A., Ortiz, L., Plotkin, S. R. Kastin, A. J. (1991) "Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism". J Pharmacol Exp Ther. 259: 988-996 They may also induce the expression of other cytokines in the brain that cause sickness behavior.Ban, E., Haour, F. Lenstra, R. (1992) "Brain interleukin 1 gene expression induced by peripheral lipopolysaccharide administration". Cytokine. 4: 48-54 van Dam, A. M., Brouns, M., Louisse, S. Berkenbosch, F. (1992) "Appearance of interleukin-1 in macrophages and in ramified microglia in the brain of endotoxin-treated rats: a pathway for the induction of non-specific symptoms of sickness?" Brain Res. 588: 291-296 Learnt The components of behavioral sickness can be learnt by conditional association such that if say a saccharin solution is given with a chemical that triggers a particular aspect of sickness behavior that on later occasions the saccharin solution will trigger it by itself.Exton, M. S., Bull, D. F. King, M. G. (1995) "Behavioral conditioning of lipopolysaccharide-induced anorexia". Physiol Behav. 57: 401-405. Exton, M. S., Bull, D. F., King, M. G. Husband, A. J. (1995) "Modification of body temperature and sleep state using behavioral conditioning". Physiol Behav. 57: 723-729. Depression It has been proposed that major depressive disorder is near-identical with sickness behavior so raising the possibility that is a maladaptive manifestation of sickness behavior due to abnormalities in circulating cytokines.Charlton, B. G. (2000) "The malaise theory of depression: major depressive disorder is sickness behavior and antidepressants are analgesic". Med Hypotheses. 54: 126-130 Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W. Kelley, K. W. (2008) "From inflammation to sickness and depression: when the immune system subjugates the brain". Nat Rev Neurosci. 9: 46-56 Cancer side effect In cancer, both the disease and the chemotherapy treatment can cause proinflammatory cytokine release which can cause sickness behavior as a side effect.Cleeland, C. S., Bennett, G. J., Dantzer, R., Dougherty, P. M., Dunn, A. J., Meyers, C. A., Miller, A. H., Payne, R., Reuben, J. M., Wang, X. S. Lee, B. N. (2003) "Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms". Cancer. 97: 2919-2925 Myers, J. S. (2008) "Proinflammatory cytokines and sickness behavior: implications for depression and cancer-related symptoms". Oncol Nurs Forum. 35: 802-807 See also * Evolutionary medicine * Health behavior * Illness behavior * Proinflammatory cytokines References Category:Symptoms Category:Evolutionary biology Category:Cytokines